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Polysaccharide derivatives and uses in induction of an immune response |
| 7595307 |
Polysaccharide derivatives and uses in induction of an immune response
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| Patent Drawings: | |
| Inventor: |
Moe, et al. |
| Date Issued: |
September 29, 2009 |
| Application: |
11/166,781 |
| Filed: |
June 23, 2005 |
| Inventors: |
Moe; Gregory R. (Alameda, CA)
Granoff; Dan M. (Berkeley, CA)
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| Assignee: |
Children's Hospital and Research Center at Oakland (Oakland, CA) |
| Primary Examiner: |
Jiang; Shaojia Anna |
| Assistant Examiner: |
Olson; Eric S |
| Attorney Or Agent: |
Francis; Carol L.Bozicevic, Field & Francis, LLP |
| U.S. Class: |
514/54; 514/55; 536/123.1 |
| Field Of Search: |
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| International Class: |
A61K 31/715; C07H 1/00; C07H 5/04 |
| U.S Patent Documents: |
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| Foreign Patent Documents: |
0504 202; WO99/10372; WO 01/09298; WO 02/09744; WO 2006/002402 |
| Other References: |
Jennings et al. 1986 J Immunol 137:1708-1713. cited by examiner.
Singh et al. 1999 Nature Biotechnology 17:1075-1081. cited by examiner.
Chapman et al. Sequential Immunization of Melanoma Patients with GD3 Ganglioside Vaccine and Anti-Idiotypic Monoclonal Antibody that Mimics GD3 Ganglioside. Clinical Cancer Research, 2004, vol. 10, 4717-4723. cited by other.
Chapman et al. Induction of IgG Antibodies Against G.sub.D3 Ganglioside in Rabbits by an Anti-idiotypic Monocloncal Antibody. Department of Medicine and the Immunology Program, 1991, 88:186-192. cited by other.
Moe et al. Epitopes Recognized by a Nonautoreactive Murine Anti-N-Propionyl Meningococcal Group B Polysaccharide Monoclonal Antibody (2005) Infect Immun 73, 2123-8. cited by other.
Moe et al. GenBank Accession Nos. DQ113491 submitted Jun. 30, 2005; ROD Mar. 8, 2006. cited by other.
Moe et al. GenBank Accession Nos. DQ113492 submitted Jun. 30, 2005; ROD Mar. 8, 2006. cited by other.
Ritter et al. Antibody Response to Immunization with Ganglioside GD3 and GD3 Congeners (Lactones, Amide and Ganliosidol) in Patients with Malignant Melanoma. Int. J. Cancer, (1991) 48, 379-385. cited by other.
Ritter et al. Analysis of the Antibody Response to Immunization with Purified O-Acetyl GD3 Gangliosides in Patients with Malignant Melanoma. Int. J. Cancer, (1995) 62, 668-672. cited by other.
Finne et al. "Occurrence of alpha 2-8 linked polysialosyl units in a neural cell adhesion molecule", 1983, Biochem Biophys Res Commun 112:482. cited by other.
Frosch et al. "NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules of Escherichia coli K1 and group B meningococci", 1985 Proc Natl Acad Sci U S A 82:1194.cited by other.
Griffiss, J. M. 1995. Mechanisms of host immunity, p. 35-70. In K. Cartwright (ed.), Meningococcal disease. John Wiley & Sons, Chichester, England. cited by other.
Granoff et al., "Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid", 1998, J. Immunol; 160: 5028-5036. cited by other.
Hurpin et al. "Bactericidal activity of two IgG.sub.2a murine monoclonal antibodies with distinct fine specificities for group B Neisseria meningitidis capsular polysaccharide", 1992 Hybridoma 11:677. cited by other.
Hayrinen et al. "Antibodies to polysialic acid and its N-propyl derivative: binding properties and interaction with human embryonal brain glycopeptides", 1995, J Infect Dis 171:1481. cited by other.
Jones D. Epidemiology of meningococcal disease in Europe and the USA. In: Cartwright K, ed. Meningococcal disease. New York: John Wiley & Sons, 1995;147-157. cited by other.
Jennings et al., "Immunochemistry of groups A, B, and C meningococcal polysaccharide-tetanus toxoid conjugates", 1981, J Immunol 127:1011. cited by other.
Mandrell et al. "Measurement of antibodies to meningococcal group B polysaccharide: low avidity binding and equilibrium binding constants", 1982 J Immunol 129:2172. cited by other.
Moreno et al. Immunological properties of monoclonal antibodies specific for meningococcal polysaccharides: the protective capacity of IgM antibodies specific for polysaccharide group B. 1983 J Gen Microbiol 129 (Pt 8):2451. cited by other.
Mandrell et al. "Complement-mediated bactericidal activity of human antibodies to poly alpha 2.fwdarw.8 N-acetylneuraminic acid, the capsular polysaccharide of Neisseria meningitidis serogroup B.", 1995 J Infect Dis 172:1279. cited by other.
Raff et al. "Human monoclonal antibody with protective activity forEscherichia coli K1 and Neisseria meningitidis group B infections", 1988 J Infect Dis 157:118. cited by other.
Rohr et al. Structure and biosynthesis of surface polymers containing polysialic acid in Escherichia coli. 1980 J Biol Chem 255:2332. cited by other.
Azmi et al. "Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1", 1994 Infect Immun 62:1776-1786. cited by other.
Ashton et al. "Protective efficacy of mouse serum to the N-propionyl derivative of meningococcal group B polysaccharide", 1989 Microb Pathog 6:455-458. cited by other.
Bruge, et al. "Clinical evaluation of a group B meningococcal N-propionylated polysaccharide conjugate vaccine in adult, male volunteers", Vaccine, 22 (2004) 1087-1096. cited by other.
Baumann, et al., "Comparison of the conformation of the epitope of .alpha.(2.fwdarw.8) polysialic acid with its reduced and N-acyl derivatives", Biochemistyr 1993, 32, 4007-4013. cited by other.
Brisson et al., "Helical eptope of the group B meningococcal .alpha.(2.fwdarw.8)-Linked sialic acid polysaccharide", Biochemistry 1992, 31, 4996-5004. cited by other.
Coquillat et al., "Activity of cross-reactivity of antibodies induced in mice by immunization with a group B meningococcal conjugate", Infect and Immun, 2001, vol. 69, No. 11, 7130-7139. cited by other.
Devi et al., "Preclinical evaluation of group B Neisseria meningitidis and Escherichia coli K92 capsular polysaccharide-protein conjugate vaccines in juvenile rhesus monkeys." 1997, Infect Immun 65:1045-52. cited by other.
Evans, et al., "Evidence for the extended helical nature of polysaccharide epitopes. The 2.8 .ANG. resolution structure and thermodynamics of ligand binding of an antigen binding fragment specific for .alpha.(2.fwdarw.8)- polysialic acid",Biochemistry, 1995, 34, 6737-6744. cited by other.
Guo et al., "Protein-polysaccaride conjugation", 2001, Humana Press Inc. p. 49-61. cited by other.
Fusco et al. "Preclinical evaluation of a novel group B meningococcal conjugate vaccine that elicits bactericidal activity in both mice and nonhuman primates," (1997) J. Infect. Dis. 175:364-72. cited by other.
Goldschneider et al., "Human Immunity to the Meningocuccus. I The Role of Humoral Antibodies", 1969, J. Exp. Med. 129:1307-1326. cited by other.
Granoff et al. "Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide eptopes that do not cross-react with human polysialic acid", 1998 J Immunol 160:5028-5036. cited by other.
Kabat, et al. "The epitope associated with the binding of the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1 to a human monoclonal macroglobulin IgMNOV", J. Exp. Med. Aug. 1, 1988;168(2):699-711. cited by other.
Hong, et al., "Inhibitory effect of K-76 monocarboxylic acid, and anticomplementary agent, on the C3b inactivator system", The J Immunol, 19981, vol. 127, No. 1, pp.104-108. cited by other.
Jennings et al., "Determinant specificities of the groups B and C polysaccharides of Neisseria meningitides", 1981, supra Jennings 1985 J Immunol 134:2651-57. cited by other.
Jennings et al. "Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine", 1986, J Immunol 137:1708-1713. cited by other.
Jennings et al. "N-propionylated group B meningococcal polysaccharide mimics a unique eptode on group B Neisseria meningitides", 1987, J Exp Med 165:1207-1211. cited by other.
Jennings et al. "Unique intermolecular bactericidal epitode involving the homosialopolysaccharide capsule on the cell surface of group B Neisseria meningitidis and Escherichia coli K1.sup.1", 1989 J Immunol 142:3585-3591. cited by other.
Lifely et al., "Immune responses in mice to different noncovalent complexes of meningococcal B polysaccharide and outer membrane proteins", Infection & Immunity, 1988, vol. 56, No. 12, p. 3221-3227. cited by other.
Lifely et al., "Sialic acid polysaccharide antigens of Neisseria meningitidis and Escherichia coli: Esterification between adjacent residues", Carbohydrate Research, 1981, 94, 193-203. cited by other.
Lifely et al., "Specificity of the immune response to the group B polysaccharide of Neisseria meningitidis", Immunology, 1991, 74, 490-496. cited by other.
Michon, et al., "Conformational differences between linear .alpha.(2.fwdarw.8)--linked homosialooligosaccharides and the epitope of the group B meaningococcal polysaccharide", Biochemistry, 1987, 26, 8399-8405. cited by other.
Moreno et al. "Immunity and protection of mice against Neisseria meningitidis group B by vaccination, using polysaccharide complexed with outer membrane proteins: a comparison with purified B polysaccharide", Infection & Immunity, 1985, vol. 47, No.2, 527-533. cited by other.
Pandey, et al, "Immunoglobulin allotypes and immune response to meningococcal group B polysaccharide", J. Clin. Invest, 1981, vol. 68, 1378-1380. cited by other.
Pon et al. "N-propionylated group B meningococcal polysaccharide mimics a unique bactericidal capsular epitope in group B Neisseria meningitidis", 1997 J Exp Med 185:1929-1938. cited by other.
R. Roy et al. "Efficient Synthesis of alpha(2-8)-linked N-Acetyl and N-Glycolylneuraminic Acid Disaccharides from Colominic Acid", Glycoconjugate Journal, vol. 7, 1990, pp. 3-12. cited by other.
Sjoberg, et al. "Expression of De-N-acetyl-gangliosides in human melanoma cells is induced by genistein or nocodazole", The journal of Biological Chemistry, 1995, vol. 270, No. 7, 2921,2930. cited by other.
Stephens et al. "Insertion of Tn916 in Neisseria meningitidis resulting in loss of group B capsular polysaccharide", 1991, Infect Immun 59:4097-4102. cited by other.
Shin et al. "Monoclonal antibodies specific for Neisseria meningitidis group B polysaccharide and their peptide mimotopes", 2001 Infect Immun 69:3335-3342. cited by other.
Wyle et al., "Immunologic response of man to group B meaningococcal polysaccharide vaccines", 1972, J. Infect. Dis. 126: 514-522. cited by other.
Zollinger, et al., "Complex of meningococcal group B polysaccharide and type 2 outer membrane protein immunogenic in man", 1979, J. Clin. Invest. 63: 836-834. cited by other.
Chammas et al. De-N-acetyl-gangliosides in Humans: Unusual Subcellular Distribution of A Novel Tumor Antigen. Cancer Research. Mar. 15, 1999, vol. 59, pp. 1337.1346, see Table 1, p. 1338, second col., p. 1343, first col., lines 7-8. cited by other.
Chapman, A. Pegylated antibodies and antibody Fragments for improved therapy: a review. Advanced Drug Delivery Reviews. 2002, vol. 54, pp. 531-545, see abstract. cited by other.
Gabri et al. Role of cell surface OM3 ganglioside and sialic acid in the antitumor activity of a GM3-based vaccine in the murine B16 melanoma model. Journal of Cancer Research and Clinical Oncology. 2002, vol. 128, pp. 669-677, see p. 670, secondcol. and p. 672, first col. cited by other.
Hellstrom et al. Strong antitumor activites of IgG3 antibodies to a human melanoma associated ganglioside. Proceeding of the National Academy of Sciences. Mar. 1985, vol. 82, pp. 1499-1502, see p. 1500 and p. 1502, first col. cited by other.
Herlyn et al, `Production and characterization of monoclonal antibodies against human malignant melanoma`, Accession No. 84129677, Abstract, Cancer Investigations, 1983, vol. I, No. 3, pp. 215-224. cited by other.
Moe et al. Epitopes Recognized by a Nonautoreactive Murine Anti-N-Propionyl Meningococcal Group B Polysaccharide Monoclonal Antibody. Infection and immunity. Apr. 2005, vol. 73, pp. 2123-2128, p. 2126, legend for figure 3, p. 2124, first col., p.2124, second col., lines 3-4 and p. 2126, second col., lines 30-31. cited by other.
Sjoberg et al. Expression of De-N-acetyl-gangliosides in Human Melanoma Cells Is Induced by Genistein or Nocodazole. The Journal of Biologilcal Chemistry. Feb. 17, 1995, vol. 270, pp. 2921-2930, see pp. 2927-2930 and p. 2924, second col., first fullparagraph. cited by other. |
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| Abstract: |
The present invention generally provides compositions comprising a polysaccharide derivative, and methods of their preparation and use for the prevention or treatment of diseases caused by Neisseria meningitidis bacteria, particularly group B (NmB) strains, and by E. coli K1. The invention provides a de-N-acetylated PS derivative in which one or more residues of the PS has been modified by de-N-acetylation. The invention also includes derivatives in which one or more of the N-acetyl groups of PS containing de-N-acetylated PS are replaced with other N-acyl groups, usually a lower acyl group of C.sub.2-C.sub.3. Further, the invention includes de-N-acetylated PS derivatives containing long chain hydrocarbons, as well as conjugates in which the de-N-acetylated PS derivative is linked to a carrier, e.g., a carrier protein. |
| Claim: |
What is claimed is:
1. A composition comprising an adjuvant and a de-N-acetylated polysaccharide (PS) derivative, wherein the de-N-acetylated PS derivative is a polysialic acid heteropolymercomprising residues of N-acetyl sialic acid, de-N-acetyl sialic acid having a free amine, and re-N-acylated sialic acid having an amine protecting group other than acetyl, and wherein said heteropolymer further comprises a minimum of about 20% N-acetylsialic acid residues and a least one dimer comprising an N-acetyl sialic acid residue and a de-N-acetyl sialic acid residue having a free amine.
2. A composition comprising a de-N-acetylated polysaccharide (PS) derivative comprising a heteropolymer of N-acetyl sialic acid, de-N-acetyl sialic acid having a free amine, and re-N-acylated sialic acid having an amine protecting group otherthan acetyl, and a structure represented by the formula: ##STR00014## wherein X and Y are independently H, an acetyl group, or an amine protecting group other than acetyl; and n is at least 1; wherein the de-N-acetylated PS derivative is conjugated toa carrier protein or further comprises a sialic acid residue having an alkyl secondary amine at a non-reducing end of the de-N-acetylated PS derivative; and wherein the de-N-acetylated PS derivative comprises a minimum of about 20% N-acetyl sialic acidresidues and at least one dimer comprising a de-N-acetyl sialic acid residue and an N-acetyl-sialic acid residue.
3. A composition comprising a polysaccharide (PS) derivative comprising a structure represented by the formula: ##STR00015## wherein X, Y and Z are independently H or a saturated acyl group, with the proviso that at least one of X, Y, and Z isH, at least one of X, Y, and Z is a saturated acyl group; and n is at least one; wherein the PS derivative is optionally conjugated to a carrier protein or further comprises a sialic acid residue having an alkyl secondary amine at a non-reducing end ofthe PS derivative, wherein said PS derivative further comprises a minimum of about 20% N-acetyl sialic acid residues and at least one dimer comprising an N-acetyl sialic acid residue and a de-N-acetyl sialic acid residue having a free amine.
4. The composition of claim 3, wherein when two of X, Y, and Z are acyl groups, the acyl groups are different acyl groups.
5. The composition of claim 4, wherein at least one of X, Y, and Z is an acetyl group and at least one of X, Y, and Z is a propionyl group.
6. The composition of claim 3, wherein when X is H, Y and Z are different acyl groups; when X is an acyl group, Y and Z are different moieties and are either H or a an acyl group; and when X is an acyl group, Y and Z are different moietiesand are either H or an acyl group.
7. The composition of claim 6, wherein when X is H, Y and Z are different acyl groups selected from acetyl and propionyl; when X is an acetyl group, Y and Z are different moieties and are either H or a propionyl group; and when X is apropionyl group, Y and Z are different moieties and are either H or an acetyl group.
8. The composition of claim 3, wherein the PS derivative comprises an amidated sialic acid residue having an alkyl secondary amine at a non-reducing terminus of the PS derivative.
9. The composition of any one of claims 1-2, wherein the de-N-acetylated PS derivative is conjugated to a carrier protein.
10. The compositions of any one of claims 1-3, wherein the PS derivative comprises a sialic acid residue derivative having a lactone moiety or a cyclic secondary amine.
11. A composition comprising a de-N-acetylated polysaccharide (PS) derivative comprising a heteropolymer of de-N-acetyl sialic acid residues, N-acetyl sialic acid residues, and re-N-acylated sialic acid residues having an amine protecting groupother than acetyl, and a structure represented by the formula: ##STR00016## wherein X and Y are independently an amine protecting group, or a saturated or unsaturated acyl group; and n is at least 1; wherein the de-N-acetylated PS derivative optionallyfurther comprises a carrier protein conjugated to a sialic acid residue of the de-N-acetylated PS derivative, or optionally further comprises an amidated sialic acid residue having an alkyl secondary amine at a non-reducing end of the de-N-acetylated PSderivative; and wherein the de-N-acetylated PS derivative comprises a minimum of about 20% N-acetyl sialic acid residues and at least one dimer comprising a de-N-acetyl sialic acid residue and an N-acetyl sialic acid residue.
12. The composition of claim 11, wherein the acyl group is a saturated acyl group selected from acetyl or propionyl.
13. The composition of claim 11, wherein the PS derivative comprises a structure represented by the formula: ##STR00017## wherein X, Y and Z are independently an amine protecting group, with the proviso that at least one of X, Y, and Z is anamine protecting group and at least one of X, Y, and Z is a saturated or unsaturated acyl group; and n is at least one.
14. The composition of claim 13, wherein the acyl group is a saturated acyl group and acetyl or propionyl.
15. A method of immunizing a subject, comprising: administering to a subject an amount of a PS derivative of claim 1 in an amount effective to elicit an immune response; wherein said administering is effective to elicit an immune response inthe subject against Neisseria meningitidis group B.
16. A method of immunizing a subject, comprising: administering to a subject an amount of a PS derivative of claim 1 in an amount effective to elicit an immune response; wherein said administering is effective to elicit an immune response inthe subject against Escherichia coli K1.
17. A method for providing passive protection against a bacterial infection, the method comprising: administering to a subject bactericidal antibodies elicited by immunization of a host with the de-N-acetylated PS derivative of any of claim 1; wherein said administering provides for protection of the subject against Neisseria meningitidis group B or against Escherichia coli K1.
18. The composition of claim 1, wherein the PS derivative comprises a structure represented by the formula: ##STR00018## wherein X, Y and Z are independently H, or a saturated or unsaturated acyl group; n is at least 1; R.sub.1 is a saturatedor unsaturated acyl amine; and R.sub.2 is a hydroxyl , one or more acylated amines, a de-N-acetylated sialic acid residue, or a polymer of de-N-acetylated sialic acid residues and acylated sialic acid residues.
19. The composition of claim 18, wherein R.sub.2 is polymer of a de-N-acetylated sialic acid residues and sialic acid residues; wherein said sialic acid residues are acetylated sialic acid residues, propionylated sialic acid residues or acombination thereof.
20. The composition of claim 1, wherein the PS derivative comprises a structure represented by the formula: ##STR00019## wherein X.sub.1, X, Y and Z are independently H, or a saturated or unsaturated acyl group; n is at least 1; R.sub.1 is asaturated or unsaturated acyl amine; and R.sub.2 is a hydroxyl, one or more acylated amines, a de-N-acetylated sialic acid residue, or polymer of de-N-acetylated sialic acid residues and acylated sialic acid residues.
21. The composition of claim 20, wherein R.sub.2 is polymer of a de-N-acetylated sialic acid residues and sialic acid residues; wherein said sialic acid residues are acetlylated sialic acid residues, propionylated sialic acid residues or acombination thereof.
22. The composition of claim 18 wherein: when X is H, Y and Z are different acyl groups selected from acetyl and propionyl; when X is an acetyl group, Y and Z are different moieties and are either H or a propionyl group; and when X is apropionyl group, Y and Z are different moieties and are either H or an acetyl group.
23. A composition comprising an adjuvant and a de-N-acetylated polysaccharide (PS) derivative, wherein the de-N-acetylated PS derivative comprises residues of N-acetyl sialic acid and de-N-acetyl sialic acid having a free amine, a minimum ofabout 20% N-acetyl sialic acid residues, and a least one dimer comprising a N-acetyl sialic acid residue and a de-N-acetyl sialic acid residue having a free amine; and wherein the de-N-acetylated PS derivative comprises a structure represented by theformula: ##STR00020## wherein n is at least 1; X and Y are independently H, or a saturated or unsaturated acyl group; R.sub.1 and R.sub.2 are independently H, or a saturated or unsaturated acyl group; and wherein the de-N-acetylated PS derivative isfurther modified to include a carrier protein and/or an acyl amine.
24. The composition of claim 23, wherein n is at least 2, X is an acetyl group, Y is an acetyl group, R.sub.1 is H, and R.sub.2 is an acetyl group.
25. The composition of claim 24, wherein the de-N-acetylated PS derivative is further modified to include a carrier protein.
26. A composition comprising an adjuvant and a de-N-acetylated polysaccharide (PS) derivative conjugated to a carrier protein, wherein the de-N-acetylated PS derivative is a polysialic acid heteropolymer that comprises residues of N-acetylsialic acid and de-N-acetyl sialic acid having a free amine, a minimum of about 20% N-acetyl sialic acid residues, and a least one dimer comprising an N-acetyl sialic acid residue and a de-N-acetyl sialic acid residue having a free amine.
27. The composition of claim 26, wherein the carrier protein is conjugated to the non-reducing end of the de-N-acetylated PS derivative.
28. The composition of claim 26, wherein the dimer comprising an N-acetyl sialic acid residue and a de-N-acetyl sialic acid residue having a free amine is at the non-reducing end of the de-N-acetylated PS derivative.
29. The composition of claim 26, wherein the de-N-acetylated PS derivative comprises a re-N-acylated sialic acid residue having an amine protecting group other than acetyl.
30. The composition of claim 26, wherein the de-N-acetylated PS derivative has degree of polymerization of about 2 to about 60.
31. The composition of claim 26, wherein the de-N-acetylated PS derivative has degree of polymerization of about 2 to about 10.
32. The composition of claim 1, wherein said de-N-acetylated PS derivative comprises an epitope recognized by the antibody SEAM 3.
33. The composition of claim 2, wherein said de-N-acetylated PS derivative comprises an epitope recognized by the antibody SEAM 3.
34. The composition of claim 11, wherein said de-N-acetylated PS derivative comprises an epitope recognized by the antibody SEAM 3.
35. The composition of claim 23, wherein said de-N-acetylated PS derivative comprises an epitope recognized by the antibody SEAM 3.
36. The composition of claim 26, wherein said de-N-acetylated PS derivative comprises an epitope recognized by the antibody SEAM 3. |
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